I will be conducting research alongside Dr. Ablonczy to scan for physical changes in retinas in response to glycation products and B-amyloid substances. Diabetic macular edema (DME) is the accumulation of fluid within the extracellular spaces of the neuroretina. DME is a principal cause of vision loss in diabates, thereby carrying enormous social and economic burdens. Early studies focused on leaky retinal blood vessels as the principal source of the edematous fluid. However, more recent data suggest that impaired fluid transport from the neuroretina by the retinal pigment epithelium (RPE) plays a critical role in the accumulation of fluid. Our long-term objective is to understand how endogenous and environmental factors impact the ability of the RPE to maintain extracellular fluid balance in the retina and prevent edema.
The pattern recognizing receptor for advanced glycation end-products (RAGE) belongs to the immunoglobulin super-family. The activation of RAGE has been shown to contribute to a variety of conditions: Alzheimer disease, cardiovascular and microvascular disorders, tumor angiogenesis, and atherosclerosis. One of the high-affinity ligands of RAGE is amyloid-42. During aging or metabolic stress, amyloid-42 is increased in ocular humors leading to the activation of RAGE in the RPE. New data from our laboratory provides evidence that RPE barrier function is compromised by amyloid-42 and that ihibition of histone acetylation reverses this response. The goal of this project is to understand the role of amyloid-42 in the breakdown of RPE fluid transport, so that we can design medications to treat diabetic macular edema.
Current treatments of DME are risky and invasive. Therefore, new approaches are required for efficient and safe pharmacological interventions to stop or reverse the condition.
Student Research Assistant
Storm Eye Institute
Medical University of South Carolina